Preventive effect of tert-butylhydroquinone on scrotal heat-induced damage in mouse testes

Li, Y.S.; Piao, Yuanguo; Nagaoka, Kentaro; Watanabe, Gen; Taya, Kazuyoshi; Li, C.M.

doi:10.4238/2013.november.11.5

Cited by 12 publications

(12 citation statements)

References 38 publications

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“…Cyp17a1 has both 17α-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Serum testosterone levels decrease, as do gene expression and activity of Cyp17a1 in the testes of mice treated with 100 mg/kg tBHQ for 7 days [53]. We also have demonstrated earlier that administration of TS-13 for 2, 4, or 7 days decreases Gstp1 expression in the liver of male mice [34].…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tert-butylhydroquinone or 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate of sodium

et al. 2017

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Tert-butylhydroquinone (tBHQ) is a highly effective phenolic antioxidant used in edible oils and fats in foods as well as in medicines and cosmetics. TBHQ has been shown to have both chemoprotective and carcinogenic effects. Furthermore, it has potential anti-inflammatory, antiatherogenic, and neuroprotective activities. TBHQ induces phase II detoxification enzymes via the Keap1/Nrf2/ARE mechanism, which contributes to its chemopreventive functions. Nonetheless, there is growing evidence that biological effects of tBHQ may be mediated by Nrf2-independent mechanisms related to various signaling cascades. Here, we studied changes in gene expression of phase I, II, and III drug metabolizing enzymes/transporters as well as protein levels and activities of cytochromes P450 (CYPs) elicited by tBHQ and its structural homolog TS-13 in the mouse liver. Next, we carried out gene expression analysis to identify signal transduction pathways modulated by the antioxidants. Mice received 100 mg/kg tBHQ or TS-13 per day or only vehicle. The liver was collected at 12 hours and after 7 days of the treatment. Protein and total RNA were extracted. Gene expression was analyzed using Mouse Drug Metabolism and Signal Transduction PathwayFinder RT2Profiler™PCR Arrays. A western blot analysis was used to measure protein levels and a fluorometric assay was employed to study activities of CYPs. Genes that were affected more than 1.5-fold by tBHQ or TS-13 treatment compared with vehicle were identified. Analysis of the gene expression data revealed changes in various genes that are important for drug metabolism, cellular defense mechanisms, inflammation, apoptosis, and cell cycle regulation. Novel target genes were identified, including xenobiotic metabolism genes encoding CYPs, phase II/III drug metabolizing enzymes/transporters. For Cyp1a2 and Cyp2b, we observed an increase in protein levels and activities during tBHQ or TS-13 treatment. Changes were found in the gene expression regulated by NFκB, androgen, retinoic acid, PI3K/AKT, Wnt, Hedgehog and other pathways.

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Section: Discussionmentioning

confidence: 84%

“…The promoter of murine Gstp1 contains 7 binding sites for androgen receptor (AR), and 3 AREs for Nrf2 [54]. The gene expression changes may be explained the possible change in the serum testosterone level, as shown elsewhere [53]. …”

Section: Discussionmentioning

confidence: 99%

The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tert-butylhydroquinone or 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate of sodium

et al. 2017

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“…Heat stress is reported to increase apoptosis in differentiating germ cells (Durairajanayagam et al, 2015;Y. Li et al, 2009;Y. S. Li et al, 2013) and so testis sections from heat-and mock-treated aged FVB males were subjected to the "Apoptag" assay and staining was quantified using FIJI software (https://fiji.sc/).…”

Section: Males Lacking Mgat4d Are More Sensitive To Mild Heat Stress mentioning

confidence: 99%

“…This protocol was adapted from (Y. S. Li et al, 2013;Rockett et al, 2001;Yin et al, 2013). Briefly, an adult male mouse was anaesthetized in an isoflurane chamber with a constant oxygen flow of 2 L/min and 3 % isoflurane for 1 min followed by 2.5 % isoflurane for 3 min.…”

Section: Mild Heat Stress Treatmentmentioning

confidence: 99%

The Golgi Glycoprotein MGAT4D is an Intrinsic Protector of Testicular Germ Cells From Mild Heat Stress

Akintayo

Liang

Bartholdy

et al. 2019

Preprint

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MGAT4D was identified as an inhibitor of MGAT1 in the Golgi of transfected cells. MGAT1 is the GlcNAc-transferase that initiates complex and hybrid N-glycan synthesis in mammals.Conditional deletion of Mgat1 in spermatogonia leads to a block in spermatogenesis and infertility in mice. Mgat4d is highly expressed in spermatocytes and spermatids. Here we show that, unexpectedly, when the Mgat4d gene was inactivated globally or conditionally in spermatogonia, or mis-expressed in spermatogonia, spermatocytes or spermatids, neither spermatogenesis nor fertility were affected. MGAT1 activity was also not inhibited in germ cells. On the other hand, when males were subjected to mild heat stress of the testis (43ºC for 25 min), a novel function for MGAT4D was revealed. Germ cells with inactivated Mgat4d were markedly more sensitive to the effects of mild heat stress, and transgenic mice expressing Mgat4d in spermatogonia, spermatocytes or spermatids were partially protected from heat stress. Microarray data from germ cells of heat-stressed mutant versus control males showed that germ cells lacking Mgat4d generally mounted a similar heat shock response to control germ cells, but could not maintain that response. Several pathways and genes activated by heat stress in wild type were induced to a lesser extent in Mgat4d[-/-] heat-stressed germ cells, including the NFk kB response, proinflammatory pathways such as TNF and TGFb signaling, and genes that promote proliferation

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“…This may further induce testicular tissue apoptosis and morphological changes affecting sperm production processes, resulting in infertility (4)(5)(6). In addition, increased scrotal temperatures resulting from occupational exposure, lifestyle or cryptorchidism are notable factors leading to male infertility (7).…”

Section: Introductionmentioning

confidence: 99%

Comparative proteomic analysis of heat stress proteins associated with rat sperm maturation

Wang

Liu

Gao

et al. 2016

Molecular Medicine Reports

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Abstract. Heat stress is demonstrated to have an effect on the function of the male testis, however, limited information has been reported on its effects on sperm maturation. In the present study, a comparative proteomic analysis was performed on the rat caput epididymal fluids responsible for sperm maturation, to identify key heat-stress-associated sperm maturation proteins. The results demonstrated 21 proteins corresponding to 29 differential protein spots, including 10 downregulated and 11 upregulated proteins in the heat treatment group. Functional analysis demonstrated that these proteins were primarily involved in enriched reproduction and antioxidant activity. Analysis of western blot and immunohistochemical analysis demonstrated that the expression of antioxidant proteins peroxiredoxin 6 and clusterin were downregulated, and the expression of superoxide dismutase upregulated, in the heat treatment group. Morphological and TUNEL experiments demonstrated that altered nucleus activity occurred in the caput epididymis. The study provided, to the best of our knowledge, novel information for studies on the biological functions of the epididymis and sperm maturation.

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Preventive effect of tert-butylhydroquinone on scrotal heat-induced damage in mouse testes

Cited by 12 publications

References 38 publications

The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tert-butylhydroquinone or 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate of sodium

The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tert-butylhydroquinone or 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate of sodium

The Golgi Glycoprotein MGAT4D is an Intrinsic Protector of Testicular Germ Cells From Mild Heat Stress

Comparative proteomic analysis of heat stress proteins associated with rat sperm maturation

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